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Serotonin 2A Receptor Gene (HTR2A) Regulatory Variants: Possible Association with Severity of Depression Symptoms in Children with Autism Spectrum Disorder

Gadow, Kenneth D. PhD*; Smith, Ryan M. PhD; Pinsonneault, Julia K. PhD

Cognitive & Behavioral Neurology: June 2014 - Volume 27 - Issue 2 - p 107–116
doi: 10.1097/WNN.0000000000000028
Hypothesis-Generating Reports

Objective and Background: Our aim was to characterize the association of 2 functional single nucleotide polymorphisms (rs6311 and rs6314) in the serotonin 2A receptor gene (HTR2A) with severity of depression symptoms in children with autism spectrum disorder. These polymorphisms have been shown to be associated with depression symptom severity and response to selective serotonin reuptake inhibitor drugs in adults with diagnosed depressive disorder.

Methods: Parents of 104 children with autism spectrum disorder rated their children’s depressive symptoms using a validated scale based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. We compared severity of depression symptoms across the rs6311 and rs6314 genotypes, measured from the children’s genomic DNA.

Results: Children homozygous for the G allele of rs6311 had significantly more severe depression symptoms than those with G/A or A/A genotypes (P=0.025). The effect size (partial eta-squared) was small (ηp2=0.047) but was somewhat larger when we controlled for severity of generalized anxiety disorder symptoms (P=0.006, ηp2=0.072). When we restricted our analyses to white participants, our results were essentially the same as for the entire sample (P=0.004, ηp2=0.086). There was no significant association between rs6314 (C/C versus T carriers) and severity of depression.

Conclusions: Our findings suggest that the HTR2A functional rs6311 polymorphism, which other studies have associated with differential HTR2A mRNA expression, may modulate the severity of depression symptoms in children with autism spectrum disorder. These tentative, hypothesis-generating findings need replication with larger, independent samples.

*Department of Psychiatry, Stony Brook University, Stony Brook, NY

Department of Pharmacology, Center for Pharmacogenomics, The Ohio State University Wexner Medical Center, Columbus, OH

Supported in part by the Matt and Debra Cody Center for Autism and Developmental Disorders, by charitable contributions, and by National Institute of General Medical Sciences Grant U01 GM092655. Wolfgang Sadee, PhD, Principal Investigator.

K.D.G. is a shareholder in Checkmate Plus, publisher of the Child Symptom Inventory-4. The remaining authors declare no conflicts of interest.

Reprints: Kenneth D. Gadow, PhD, Department of Psychiatry, Stony Brook University, Stony Brook, NY 11794-8790 (e-mail: kenneth.gadow@stonybrook.edu).

Received May 13, 2013

Accepted October 17, 2013

© 2014 by Lippincott Williams & Wilkins.